Network pharmacology integrated molecular dynamics reveals the bioactive compounds and potential targets of Tinospora crispa Linn. as insulin sensitizer.

Abstract

Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and β sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.